Copper-catalyzed carbonylative multi-component borylamidation of alkenes for synthesizing γ-boryl amides with CO as both methylene and carbonyl sources.

A multi-component carbonylation reaction is an efficient strategy for the synthesis of valuable carbonyl compounds from simple and readily available substrates. However, there remain challenges in carbonylation reactions where two CO molecules are converted to different groups in the target product. Considering the merit of complex amides, we reported here a copper-catalyzed multi-component borylamidation for the synthesis of γ-boryl amides. This method provides access to a wide range of functional γ-boryl amides from alkenes, amines, B2pin2, and CO with good yields and excellent diastereomeric ratios. Notably, two CO molecules were converted to methylene and carbonyl groups in the target amides. A series of amines were successfully involved in the transformation, including arylamines, aliphatic amines, and hydrochloride salts of secondary aliphatic amines.

Copper-catalyzed synthesis of ß-boryl cyclopropanes via 1,2-borocyclopropanation of aryl olefins with CO as the C1 source.

Cyclopropane represents one of the most critical rings and has been found present in various bioactive compounds, especially in clinical medicines. It can be synthesized by the reaction of olefins with diazo-derived carbenoids which are potentially hazardous. Carbonylation is a powerful tool for synthesizing carbonylated or carbon-extended compounds. In this communication, we describe a straightforward approach for synthesizing ß-boryl cyclopropane derivatives catalyzed by an inexpensive copper catalyst with CO as the C1 source. This reaction was mediated by an in situ generated carbene intermediate and afforded a wide range of cyclopropane-containing organoboron compounds in moderate to good yields.

Copper-catalyzed defluorinative arylboration of vinylarenes with polyfluoroarenes.

An unprecedented but challenging defluorinative arylboration has been achieved. Enabled by a copper catalyst, an interesting procedure on defluorinative arylboration of styrenes has been established. With polyfluoroarenes as the substrates, this methodology offers flexible and facile access to provide a diverse assortment of products under mild reaction conditions. In addition, by using a chiral phosphine ligand, an enantioselective defluorinative arylboration was also realized, affording a set of chiral products with unprecedented levels of enantioselectivity.

Copper-Catalyzed Synthesis of Multideuterium-Labeled Alcohols from Styrenes with CO and D2 as the Source of the Hydroxymethyl Group.

Deuterated compounds have important applications, especially in the pharmaceutical field. Hence, the development of new and straightforward synthetic methods for the construction of deuterated compounds is becoming more and more attractive. We describe here a copper-catalyzed hydroxymethylation of aryl olefins with CO and D2 as the source of hydroxymethyl group. Various multideuterium 1,1,2,3-d4-labeled alcohols were produced directly. Mechanistic investigations established that the hydroxymethylation reaction proceeds via an in situ-generated carbon carbene intermediate.

Copper-Catalyzed Boroaminomethylation of Olefins to γ-Boryl Amines with CO as C1 Source.

Boroaminomethylation of olefins is an efficient process to convert hydrocarbons directly into boron-, nitrogen-containing molecules. Such chemicals are a good handle for obtaining more complexed amine derivatives through the various transformations of organoboron. However, using simple and easily available CO as the C1 feedstock to achieve boroaminomethylation is still elusive. Here we report a copper-catalyzed boroaminomethylation of olefins with CO as the C1 source via the mechanism of a carbene insertion into the N-H bond. This method affords valuable γ-boryl amines from four inexpensive readily chemicals. The wide synthetic transformations of the γ-boryl amines demonstrates their utility. Notably, 13 C labeling studies revealed that the -CH2 -building block was derived from one molecule of CO.

Copper-catalyzed hydroaminocarbonylation of benzylidenecyclopropanes: synthesis of γ,δ-unsaturated amides.

Herein, we have developed a copper-catalyzed hydroaminocarbonylation of benzylidenecyclopropanes under relatively mild conditions. A series of γ,δ-unsaturated amides with a broad range of functional groups were obtained in moderate to good yields. Both dialkyl-substituted and monoalkyl-substituted hydroxylamine derivatives can be applied in this transformation to give the corresponding tertiary and secondary amides successfully.

Copper-catalyzed hydroformylation and hydroxymethylation of styrenes.

Hydroformylation catalyzed by transition metals is one of the most important homogeneously catalyzed reactions in industrial organic chemistry. Millions of tons of aldehydes and related chemicals are produced by this transformation annually. However, most of the applied procedures use rhodium catalysts. In the procedure described here, a copper-catalyzed hydroformylation of alkenes has been realized. Remarkably, by using a different copper precursor, the aldehydes obtained can be further hydrogenated to give the corresponding alcohols under the same conditions, formally named as hydroxymethylation of alkenes. Under pressure of syngas, various aldehydes and alcohols can be produced from alkenes with copper as the only catalyst, in excellent regioselectivity. Additionally, an all-carbon quaternary center containing ethers and formates can be synthesized as well with the addition of unactivated alkyl halides. A possible reaction pathway is proposed based on our results.

Copper-Catalyzed Alkoxycarbonylation of Alkyl Iodides for the Synthesis of Aliphatic Esters: Hydrogen Makes the Difference.

A copper-catalyzed alkoxycarbonylation transformation of unactivated alkyl iodides has been developed. Various alkyl iodides can be converted into the corresponding tert-butyl esters in good yields. NaOtBu acts as both a nucleophile and a base. Moreover, other types of aliphatic esters can also be obtained in moderated yields if extra alcohols are added. Both primary and secondary alkyl alcohols can react successfully.

Palladium-Catalyzed Carbonylative Four-Component Synthesis of ß-Perfluoroalkyl Amides.

Transition-metal-catalyzed multicomponent carbonylation is one of the most efficient strategies to construct carbonyl-containing compounds. Herein, a palladium-catalyzed four-component perfluoroalkylation/aminocarbonylation of unactivated alkenes with perfluoroalkyl halides, and amines was developed. A wide range of substrates, including anilines, alkylamines, sulfonamides, and hydrazines are all suitable reaction partners for this catalyst system, resulting in various ß-perfluoroalkyl amides with good functional-group tolerance and excellent chemoselectivity. Furthermore, not only alkyl olefins, but also aliphatic alkynes, and even alkyl allenes can all be employed. Notably, several medical and bioactive related molecules are compatible here as well.

Palladium-Catalyzed Perfluoroalkylative Carbonylation of Unactivated Alkenes: Access to ß-Perfluoroalkyl Esters.

Transition-metal-catalyzed multi-component carbonylation represents an efficient strategy for the preparation of various functionalized carbonyl-containing compounds. Herein, we report a general palladium-catalyzed perfluoroalkylative carbonylation of unactivated alkenes using inexpensive and readily available carbon monoxide as the C1 source and perfluoroalkyl halides as the coupling partner. A wide range of phenols and alcohols were transformed into the corresponding ß-perfluoroalkyl esters in high yields with broad functional group tolerance and good chemoselectivity. Additionally, alkyl halides can be utilized as alkoxy source as well to give the desired esters. Moreover, several pharmaceutical and bio-active molecules were also suitable substrates for this one-pot multi-component carbonylation process to give the targeted products in good yields.

Palladium-Catalyzed Carbonylative Synthesis of α-Branched Enones from Aryl Iodides and Arylallenes.

In this communication, an interesting carbonylation protocol for the preparation of α-branched enones has been established. Starting from readily available aryl iodides and allenes, with formic acid as the CO source and reductant, moderate to good yields of the desired enones were isolated. Although it is a carbonylation methodology, the use of a CO source can avoid the manipulation of CO gas directly. Notably, this procedure also presents the first example on carbonylative synthesis of α-branched enones.

Palladium-Catalyzed Oxidative Carbonylative Coupling of Arylallenes, Arylboronic Acids, and Nitroarenes.

In this Letter, a palladium-catalyzed multicomponent procedure for the selective synthesis of α-substituted α,ß-unsaturated ketones has been developed. With readily available allenes, arylboronic acids, and nitroarenes as the substrates, the reaction proceeds selectively to the desired α-substituted enones. Notably, no manipulation of carbon monoxide gas is needed here, and Mo(CO)6 has been applied as a stable solid CO source instead. Additionally, as an oxidative coupling reaction, nitroarenes are used as both the amine source and the oxidant to regenerate the active palladium species.

Palladium-Catalyzed Amide Synthesis via Aminocarbonylation of Arylboronic Acids with Nitroarenes.

A palladium-catalyzed aminocarbonylation of aryl boronic acids with nitroarenes for the synthesis of amides has been developed. A wide range of substrates were well-tolerated and gave the corresponding amides in moderate to good yields. No external oxidant or reductant was needed in this procedure. This procedure provides a redox-economical process for the synthesis of amides.

Palladium-Catalyzed Carbonylative Synthesis of α,ß-Unsaturated Amides from Styrenes and Nitroarenes.

A procedure on palladium-catalyzed selective aminocarbonylation of styrenes with nitroarenes for the synthesis of α,ß-unsaturated amides has been developed. A range of substituted α,ß-unsaturated amides were synthesized in moderate to good yields. Interestingly, nitroarenes act as both a nitrogen source and oxidant, and Mo(CO)6 acts as a solid CO source and reductant in this catalytic system.